Recently, gastric mucosa has been shown to actively secrete bicarbonate (HCO3-) into the lumen. This observation leads to a hypothesis that active secretion of HCO3- may be another important cytoprotective mechanism of the gastric mucosa, since the secreted HCO3-is likely to neutralize the intraluminal acid at the mucosal surface. To assess this hypothesis, the proposed studies are designed (1) to evaluate the role of HCO3- secretion on the acid-base status of the mucosa by measuring intramural pH and (2) to examine the changes in the rate of HCO3- secretion following various stimuli. They include (1) acetylsalicylic acid, a known gastric irritant, (2) Prostaglandin E2, a cytoprotective agent against experimental ulcerations, and (3) ischemia, a predisposing factor in acute ulcerogenesis. In addition, the following studies will determine if HCO3- secretion is affected by secretagogues such as acetylcholine, histamine and pentagastrin and/or mediated by cGMP. The experimental model for these studies will be an in vivo canine stomach which permits the calculation of HCO3- secretion by measuring intragastric pCO2 and pH as described by Garner and Flemstrom. This technique will be added to our present ability to measure gastric blood flow by gamma-labeled microspheres, mucosal cGMP by radioimmunoassay and intramural pH by the microelectrode technique.